多学科联合诊治儿童头颈部横纹肌肉瘤48例临床研究

Clinical study on 48 children with head and neck rhabdomyosarcoma treated by multi-disciplinary therapy

目的总结多学科联合诊治儿童头颈部横纹肌肉瘤(RMS)的近期疗效,分析其预后相关因素,以指导诊疗。方法采用病例观察研究,选择2012年12月至2017年5月首都医科大学附属北京儿童医院血液肿瘤中心收治的头颈部RMS患儿为研究对象,分析其临床特征,总结治疗效果及预后影响因素。结果共48例患儿纳入本研究,男36例,女12例,中位年龄4.6岁。48例患儿原发部位:脑膜旁区34例(70.8%),眼眶2例(4.2%),非眼眶、非脑膜旁12例(25.0%)。腺泡型20例(41.7%),胚胎型28例(58.3%);肿瘤直径>5 cm 25例(52.1%),≤5 cm 23例(47.9%);国际横纹肌肉瘤研究组(IRS)分期:Ⅱ~Ⅲ期29例(60.4%),Ⅳ期19例(39.6%);低中危组29例(60.4%),高危组19例(39.6%);行手术切除瘤灶或部分切除23例(47.9%),仅活检25例(52.1%)。48例患儿均行全身化疗,未放疗3例(6.2%),外放疗20例(41.6%),质子治疗6例(12.5%),125I粒子植入治疗15例(31.3%),2种以上局部控制措施4例(8.3%)。随访13~57个月[(24.1±12.3)个月],2年总生存率(OS)为(66.4±7.2)%,2年无事件生存率(EFS)为(59.9±7.5)%。肿瘤直径≤5 cm者2年OS、EFS显著高于肿瘤直径>5 cm者[2年OS (87.4±6.8)%比(42.9±6.8)%,2年EFS (78.8±8.6)%比(38.5±10.8)%],差异均有统计学意义(均P=0.006)。肿瘤原发于眼眶及非眼眶、非脑膜旁者2年OS、EFS均显著高于肿瘤原发于脑膜旁者[2年OS 100.0%比(87.5%±11.7)%比(57.0±8.8)%,2年EFS 100.0%比(88.9±10.5)%比(51.1±8.9)%],差异均有统计学意义(P=0.008、0.030)。有机会手术切除者2年OS、EFS均显著高于无法手术切除者[2年OS (80.7±8.8)%比(53.3±10.4)%,2年EFS (71.1±10.1)%比(49.5±10.4)%],差异均有统计学意义(P=0.008、0.026)。多因素COX回归分析显示,肿瘤直径>5 cm是预后不良因素(OR=4.124,95%CI:1.213~14.025,P=0.023)。结论RMS中脑膜旁区所占比例高。肿瘤原发部位及瘤灶大小是影响预后的主要因素。强化疗方案有望改善伴脑膜侵犯征象RMS患儿的预后。

Objective To explore the short-term efficacy in children with head and neck rhabdomyosarcoma (HN-RMS) treated by multidisciplinary therapy, and to analyze the prognostic factors, so as to guide the diagnosis and treatment. Methods Patients with HN-RMS admitted at Hematology Oncology Center of Beijing Children′s Hospital (BCH), Capital Medical University between December 2012 and May 2017, were included in this case-observation study.The clinical characteristics were analyzed and the treatment effect and prognostic factors were summarized. Results A total of 48 cases were collected, including 36 boys and 12 girls, with a median age of 4.6 years.Primarysite parameningeal RMS(PM-RMS)(34 cases, 70.8%), orbital(2 cases, 4.2%) and non-orbital, non-parameningeal region(12 cases, 25.0%) were found.Twenty cases belonged to alveolar type(41.7%), and 28 cases were of embryonal type(58.3%). The diameter of the tumor was >5 cm(n=25, 52.1%), and ≤5 cm(n=23, 47.9%). IRS staging: there were 29 cases(60.4%) of stage Ⅱ-Ⅲ, 19 cases(39.6%) of stage Ⅳ;29 cases(60.4%) of low-medium risk, and 19 cases(39.6%) of high risk.Twenty-three patients(47.9%) received surgery, and 25 cases (52.1%) received biopsy only.All patients (48 cases) received systemic chemotherapy.Twenty patients(41.6%) received external radiation, 15 cases (31.3%)received 125I particle implantation, 6 cases (12.5%)received proton therapy, but 3 cases (6.2%)did not receive radiation.The follow-up time lasted 13-57 months[(24.1±12.3) months]. The 2-year overall survival(OS) rate was (66.4±7.2)%, and 2-year event free survival (EFS) rate was (59.9±7.5)%.Patients with tumor diameter ≤5 cm had higher OS and EFS than patients with tumor diameter >5 cm [2-year OS (87.4±6.8)% vs.(42.9±6.8)%, 2-year EFS (78.8±8.6%) vs.(38.5±10.8)%], and the differences were statistically significant (all P=0.006). Patients with orbital and non-orbital, non-parameningeal RMS had higher OS and EFS than PM-RMS [2-year OS 100% vs.(87.5%±11.7)% vs.(57.0±8.8)%;2-year EFS 100% vs.(88.9±10.5)% vs.(51.1±8.9)%], and the differences were statistically significant (P=0.008, P=0.030). Patients who received surgery had higher OS and EFS than those who did not received surgery[2-year OS (80.7±8.8)% vs.(53.3±10.4)%;2-year EFS (71.1±10.1)% vs.(49.5±10.4)%], and the differences were statistically significant (P=0.008, P=0.026). COX regression analysis showed tumor diameter >5 cm was an adverse prognostic factor (OR=4.124, 95%CI: 1.213-14.025, P=0.023). Conclusions PM-RMS accounted for a high proportion in RMS patients.The primary site and the size of the tumor are the main prognostic factors.Intensive therapy is expected to improve the prognosis of HN-RMS with meningeal invasion.